Pasotuxizumab, a BiTE® immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings

Immunotherapy. 2021 Feb;13(2):125-141. doi: 10.2217/imt-2020-0256. Epub 2020 Nov 10.

Abstract

Aim: We report results of a first-in-human study of pasotuxizumab, a PSMA bispecific T-cell engager (BiTE®) immune therapy mediating T-cell killing of tumor cells in patients with advanced castration-resistant prostate cancer. Patients & methods: We assessed once-daily subcutaneous (SC) pasotuxizumab. All SC patients developed antidrug antibodies; therefore, continuous intravenous (cIV) infusion was assessed. Results: A total of 47 patients received pasotuxizumab (SC: n = 31, 0.5-172 μg/d; cIV: n = 16, 5-80 μg/d). The SC maximum tolerated dose was 172.0 μg/d. A sponsor change stopped the cIV cohort early; maximum tolerated dose was not determined. PSA responders occurred (>50% PSA decline: SC, n = 9; cIV, n = 3), including two long-term responders. Conclusion: Data support pasotuxizumab safety in advanced castration-resistant prostate cancer and represent evidence of BiTE monotherapy efficacy in solid tumors. Clinical trial registration: NCT01723475 (ClinicalTrials.gov).

Keywords: AMG 212; BAY 2010112; PSMA; bispecific T-cell engager (BiTE®) immune therapy; pasotuxizumab; prostate cancer.

Publication types

  • Clinical Trial, Phase I
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Bispecific* / immunology
  • Antibodies, Bispecific* / pharmacokinetics
  • Antibodies, Bispecific* / therapeutic use
  • Antigens, Surface / immunology
  • Antineoplastic Agents, Immunological* / immunology
  • Antineoplastic Agents, Immunological* / pharmacokinetics
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Biomarkers, Tumor / blood
  • CD3 Complex / immunology
  • Glutamate Carboxypeptidase II / immunology
  • Humans
  • Immunotherapy
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Prostatic Neoplasms, Castration-Resistant* / blood
  • Prostatic Neoplasms, Castration-Resistant* / immunology
  • Prostatic Neoplasms, Castration-Resistant* / pathology
  • Prostatic Neoplasms, Castration-Resistant* / therapy
  • Treatment Outcome

Substances

  • Antibodies, Bispecific
  • Antigens, Surface
  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • CD3 Complex
  • FOLH1 protein, human
  • Glutamate Carboxypeptidase II
  • Pasotuxizumab

Associated data

  • ClinicalTrials.gov/NCT01723475